| Eligibility |
Inclusion Criteria:
1. Be age 18 years or older and has read, understood, and provided written informed
consent and, if applicable, Health Insurance Portability and Accountability Act
(HIPAA) authorization after the nature of the study has been fully explained and must
be willing to comply with all study requirements and procedures.
2. Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma with
metastatic disease.
3. Agree to be tested for peripheral blood levels of IgG anti-beta-glucan antibody (ABA)
as determined by an ELISA test prior to start of study treatment.
4. Have received a minimum of 16 weeks and no more than 32 weeks of therapy (first-line
chemotherapy) and experienced a CR, PR, or SD with no evidence of progression
immediately before enrollment (within 14 days of first dose).
a. Note: this requires at least durable stability or a reduction in tumor size by
imaging. If a patient has demonstrated an imaging response to chemotherapy and has not
progressed but had to discontinue chemotherapy prior to 16-32 weeks for a legitimate
medical reason (as determined by the investigator), the patient may still be
considered for the trial.
5. Have resolution of all chemotherapy-related toxicities to pre-treatment levels with
exception of alopecia (which can be ongoing) and neuropathy (which can be = Grade 2).
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the
time of screening.
7. Have the following laboratory values, without transfusions or growth factors, at
Screening and within 14 days of the first dose of investigational agents:
1. White blood cell count =2000/uL
2. Absolute neutrophil count (ANC) =1.5 x 109/L.
3. Platelet count =100 x 109/L.
4. Hemoglobin =9 g/dL.
5. Serum creatinine =1.5 mg/dL, and creatinine clearance =50 ml/min as measured by
Cockcroft and Gault formula.
6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 x
institution's ULN for patients with no concurrent liver metastases, OR =5.0 x
institution's ULN for patients with concurrent liver metastases.
7. Total bilirubin =1.5 x ULN, except in patients with documented Gilbert's Syndrome
who must have a total bilirubin =3 x ULN.
8. Serum albumin of at least 3 g/dL.
8. Have adequate coagulation function within 14 days prior to first administration of
study drug on
Day 1, as defined by either of the following criteria:
1. International normalized ratio (INR) <1.5 × ULN OR for patients receiving
warfarin or low molecular weight heparin, the patient must, in the investigator's
opinion, be clinically stable with no evidence of active bleeding while receiving
anticoagulant therapy. The INR for these patients may exceed 1.5 × ULN if that is
the goal of anticoagulant therapy
2. Activated partial thromboplastin time (aPTT) <1.5 × ULN unless patient is
receiving anticoagulant therapy, provided prothrombin time or aPTT is within
therapeutic range of intended use of anticoagulants.
9. Women of childbearing potential (WOCBP) must have a negative pregnancy test (serum or
urine) within the 7 days prior to study drug administration, and a negative urine
pregnancy test within the 3 days before the first study drug administration, or a
negative serum pregnancy test within 24 hours before the first study drug
administration.
10. WOCBP and male patients who are sexually active with WOCBP must agree before receiving
the first dose of study drugs to use 2 highly effective methods of contraception
(including a physical barrier) during the study and for 120 days after the last dose
of study drug, as described in the body of the protocol.
11. Patients must have the ability to understand and willingness to sign a written
informed consent document.
Exclusion Criteria:
1. Previous exposure to odetiglucan (Imprime PGG).
2. Previous exposure to CD40 antibodies or any other immunomodulatory agent for the
treatment of cancer.
3. Received chemotherapy within the 14 days prior to initiation of study treatment.
a. Concomitant antineoplastic systemic chemotherapy or biological therapy is not
allowed.
4. A history of (non-infectious) pneumonitis / interstitial lung disease or has current
pneumonitis / interstitial lung disease including grade 1 asymptomatic pneumonitis
noted on imaging not requiring treatment.
5. Had any active or inactive autoimmune disease or syndrome (i.e., rheumatoid arthritis,
moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease) that
required systemic treatment in the past 2 years or who are receiving systemic therapy
for an autoimmune or inflammatory disease (i.e., with use of disease modifying agents,
corticosteroids, or immunosuppressive drugs).
a. Note: Exceptions include patients with vitiligo or resolved childhood asthma/atopy,
hypothyroidism stable on hormone replacement, controlled asthma, Type I diabetes,
Graves' disease, or Hashimoto's disease, or with medical monitor approval.
6. An uncontrolled concurrent illness, including an ongoing or active infection,
symptomatic congestive heart failure (New York Heart Association class III or IV),
unstable angina, uncontrolled hypertension, cardiac arrhythmia, interstitial lung
disease or uncontrolled diabetes.
7. QT interval corrected for heart rate using Fridericia's (QTcF) method >450 msec for
males and >460 msec for females.
8. A history of myocardial infarction within 6 months or a history of arterial
thromboembolic event within 3 months of the first dose of investigational agent.
9. A history of human immunodeficiency virus (HIV), hepatitis B (HB), or hepatitis C,
except for the following:
1. Patients with anti-HB core antibody but with undetectable HB virus
deoxyribonucleic acid (DNA) and negative for HB surface antigen
2. Patients with resolved or treated hepatitis C virus (HCV) (i.e., HCV antibody
positive but undetectable HCV RNA).
10. Received concurrent or prior use of an immunosuppressive agent within 14 days of the
first dose of investigational agent, with the following exceptions and notes:
1. Systemic steroids at physiologic doses (equivalent to dose of 10 mg oral
prednisone) are permitted.
2. Intranasal, inhaled, topical intra-articular, and ocular corticosteroids with
minimal systemic absorption are permitted.
3. Transient course of steroids may be approved by the Medical Monitor on a case by
case basis, dependent on dose, timing and reason.
11. Active, untreated central nervous system (CNS) metastases or a history of clinically
manifested central nervous system (CNS) metastases.
a. Note: Patients with brain metastases identified at Screening may be rescreened
after the lesion(s) have been appropriately treated; patients with treated brain
metastases should be neurologically stable for 4 weeks post-treatment and prior to
study enrollment, and off corticosteroids for at least 2 weeks before administration
of study drugs, and treated lesions should demonstrate no new growth on the
re-screening scan
12. Known or suspected leptomeningeal disease or cord compression. Product: Odetiglucan
and CDX-1140 11 Protocol/Amendment No.: PGG-PAN2111, Amd.000 Confidential - HiberCell
Inc.
13. Had major surgery as determined by the investigator within 4 weeks before the first
dose of study drug. Surgery requiring local/epidural anesthesia must be completed at
least 72 hours before study drug administration and patients should be recovered.
14. Other prior malignancy, except for adequately treated basal or squamous cell skin
cancer or in situ cancers; or any other cancer from which the patient has been
disease-free for at least 3 years.
15. Received another investigational agent within the shorter of 4 weeks or 5 half-lives
before the first dose of investigational agents.
16. Received a live attenuated vaccine within 28 days before the first dose of
investigational agent, and patients, if enrolled, should not receive live vaccines
during the study or for 30 days after the last dose of investigational agent.
17. Females who are pregnant or lactating or who intend to become pregnant during
participation in the study are not eligible to participate.
18. Known alcohol or drug abuse.
19. Any clinically significant psychiatric, social, or medical condition that, in the
opinion of the investigator, could increase the patient's risk, interfere with
protocol adherence, or affect the patient's ability to give informed consent.
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